It is clear that nervous system changes contribute significantly to human aging, and histological signs of aging can be found in the nervous systems of aged animals. However, there is presently no clear picture of the temporal sequence of biochemical changes occurring in an aging brain. We propose to use random samples chosen at various ages from a large population of mice and rats in order to follow the development, maturation and aging of several regions of the brain. For this purpose we have selected a series of biochemial assays which measure membrane- related functions of the nervous system, and nerve cell metabolism. The assays to be used include tetrodotoxin binding, ouabain binding, alpha-bungarotoxin binding, choline acetylase, 2',3'-cyclic nucleotide 3'phosphohydrolase, thymidine kinase, cytochrome c oxidase, catalase, and acid phosphatase. These assays will be applied to telencephalon, cerebellum, and brain stem of normal mice throughout their lifespan, and to two strains of neurological mutants: Jimpy, which has a very short lifespan; and Quaking, which has a normal lifespan. The same assays will also be applied to adult and senescent rats, in which it will be possible to dissect several neuroanatomical structures for a more detailed examination of regional differences in brain biochemistry during aging. This project will produce an integrated body of data on biochemical changes in different brain regions, and should facilitate the development of biochemical criteria of aging.